MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium
Abstract Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validati...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Nature Portfolio
2018-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-27740-3 |
| _version_ | 1818753910252240896 |
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| author | Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy |
| author_facet | Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy |
| author_sort | Bence Ágg |
| collection | DOAJ |
| description | Abstract Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart. |
| first_indexed | 2024-12-18T05:14:52Z |
| format | Article |
| id | doaj.art-13fda4bbf4064b339b6972ee7ccd3d94 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:14:52Z |
| publishDate | 2018-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-13fda4bbf4064b339b6972ee7ccd3d942022-12-21T21:19:47ZengNature PortfolioScientific Reports2045-23222018-07-018111110.1038/s41598-018-27740-3MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardiumBence Ágg0Tamás Baranyai1András Makkos2Borbála Vető3Nóra Faragó4Ágnes Zvara5Zoltán Giricz6Dániel V. Veres7Péter Csermely8Tamás Arányi9László G. Puskás10Zoltán V. Varga11Péter Ferdinandy12Department of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityInstitute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of SciencesInstitute of Genetics, Biological Research Center of the Hungarian Academy of SciencesInstitute of Genetics, Biological Research Center of the Hungarian Academy of SciencesDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Medical Chemistry, Semmelweis UniversityDepartment of Medical Chemistry, Semmelweis UniversityInstitute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of SciencesInstitute of Genetics, Biological Research Center of the Hungarian Academy of SciencesDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityAbstract Little is known about the molecular mechanism including microRNAs (miRNA) in hypercholesterolemia-induced cardiac dysfunction. We aimed to explore novel hypercholesterolemia-induced pathway alterations in the heart by an unbiased approach based on miRNA omics, target prediction and validation. With miRNA microarray we identified forty-seven upregulated and ten downregulated miRNAs in hypercholesterolemic rat hearts compared to the normocholesterolemic group. Eleven mRNAs with at least 4 interacting upregulated miRNAs were selected by a network theoretical approach, out of which 3 mRNAs (beta-2 adrenergic receptor [Adrb2], calcineurin B type 1 [Ppp3r1] and calcium/calmodulin-dependent serine protein kinase [Cask]) were validated with qRT-PCR and Western blot. In hypercholesterolemic hearts, the expression of Adrb2 mRNA was significantly decreased. ADRB2 and PPP3R1 protein were significantly downregulated in hypercholesterolemic hearts. The direct interaction of Adrb2 with upregulated miRNAs was demonstrated by luciferase reporter assay. Gene ontology analysis revealed that the majority of the predicted mRNA changes may contribute to the hypercholesterolemia-induced cardiac dysfunction. In summary, the present unbiased target prediction approach based on global cardiac miRNA expression profiling revealed for the first time in the literature that both the mRNA and protein product of Adrb2 and PPP3R1 protein are decreased in the hypercholesterolemic heart.https://doi.org/10.1038/s41598-018-27740-3 |
| spellingShingle | Bence Ágg Tamás Baranyai András Makkos Borbála Vető Nóra Faragó Ágnes Zvara Zoltán Giricz Dániel V. Veres Péter Csermely Tamás Arányi László G. Puskás Zoltán V. Varga Péter Ferdinandy MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium Scientific Reports |
| title | MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium |
| title_full | MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium |
| title_fullStr | MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium |
| title_full_unstemmed | MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium |
| title_short | MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium |
| title_sort | microrna interactome analysis predicts post transcriptional regulation of adrb2 and ppp3r1 in the hypercholesterolemic myocardium |
| url | https://doi.org/10.1038/s41598-018-27740-3 |
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